The elevated glucose levels seen in pre-diabetes, gestational diabetes, and established diabetes can affect protein biomarkers found in biological fluids. For example, glycemic control may affect direct, non-enzymatic protein glycation in which glucose becomes covalently linked to target proteins through the formation of a Schiff base between the aldehyde group of the glucose molecule and the amino group of a lysine residue in a protein. The Schiff base then undergoes an Amadori rearrangement and oxidation to form an advanced glycation end product. One example of an advanced glycation end product is hemoglobin A1c (HbA1c). The blood levels of HbA1c represent the average blood glucose (BG) level over the previous 3 months, reflecting the lifespan of the red blood cells that carry hemoglobin.
There are a number of issues that arise with using HbA1c to monitor glucose homeostasis, including its inability to reflect shorter-term variations in BG, significant genetic and non-glycemic effects on HbA1c levels, and significant age-dependent and ethnic variations in the relationship between HbA1c levels and average BG levels. The use of glycated albumin or fructosamine as an alternative offers the advantage of reflecting a shorter response time (e.g., representing the average BG level over the previous 2-4 weeks), but the effects of the various factors that hamper the utility of HbA1c on the relationship between these glycated proteins and previous BG levels remain problematic.